This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nearly two-thirds of diabetics suffer from overt cardiovascular conditions, including coronary artery disease, myocardial infarction (MI), and cardiomyopathy. Despite the known systemic nature of diabetes, therapy for MI and ischemic cardiomyopathy are often not specifically tailored for diabetics, and the feasibility and efficacy of stem cell therapy for infarct repair in diabetic patients remains unclear. Although mesenchymal stem cells (MSCs) have been shown to induce infarct repair, the results have been variable and mechanisms remain controversial. The variability in MSC-mediated cardiac repair might have stemmed from the fundamentally heterogeneous nature of unfractionated 'MSCs'. We hypothesize that the use of a homogenous antigenically-defined MSC subpopulation with greater endothelial and cardiomyogenic differentiation potential and greater ability to secrete cardioprotective factors will result in superior cardiac repair in diabetics. These studies will identify the best MSC to use for infarct repair specifically in diabetics, and the results would have enormous therapeutic implications for diabetic patients with ischemic heart disease and post-MI heart failure.